Systems and Methods for Introducing and Applying a Bandage Structure Within a Body Lumen or Hollow Body Organ

ABSTRACT

Systems and methods provide intraluminal delivery of a bandage structure within a body lumen or hollow body organ, e.g., for treating an injured gastrointestinal tract or an esophageal hemorrhage in a non-invasive way using endoscopic visualization. The systems and methods can be sized and configured to apply a chitosan bandage structure within a body lumen or hollow body organ, to take advantage of the mucoadhesive, antimicrobial, hemostatic, and potential accelerated wound healing properties of the chitosan material.

RELATED APPLICATIONS

This application is a continuation of copending patent application Ser.No. 12/004,297, filed Dec. 20, 2007, which itself is a continuation ofpatent application Ser. No. 11/805,543 filed May 23, 2007, nowabandoned, which claims the benefit of provisional patent applicationSer. No. 60/802,654 filed 23 May 2006.

This application is related to U.S. patent application Ser. No.11/084,688, filed on Mar. 17, 2005, entitled “Systems and Methods forHemorrhage Control and/or Tissue Repair.”

FIELD OF THE INVENTION

The invention is generally directed to systems and methods to introduceand deploy tissue bandage structures within a body lumen or hollow bodyorgan, such, e.g., as within the gastrointestinal tract.

BACKGROUND OF THE INVENTION

Currently, there exists no overwhelmingly accepted treatment forgastrointestinal, specifically esophageal bleeding with etiology suchas; esophageal ulcers, esophagitis, Mallory Weis tears, Booerhave'ssyndrome, esophageal varices, anastornosis, fistula, and endoscopicprocedures.

Electro-cautery and sclerotherapy are two existing treatments foresophageal hemorrhage; however both run a risk of perforation to theesophagus. Electro-cautery requires a large amount of pressure to beapplied to the wall of the esophagus and also inherently damages tissue.Sclerotherapy consists of injecting a hardening agent in to the area ofthe injury with a needle. Clipping is another method of treatment; itconsists of a two or three-pronged clip that can be inserted into themucosa of the esophagus to constrict the area of the bleeding. Ifapplied correctly, clipping is effective in controlling hemorrhage,however clips are difficult to deploy. Often, the clip is not inserteddeep enough into the mucosa and sloughs off before the desired time.

SUMMARY OF THE INVENTION

The invention provides systems and methods for applying a bandagestructure within a body lumen or a hollow body organ, e.g., for treatingan injured gastrointestinal tract or an esophageal hemorrhage.

Another aspect of the invention includes systems and methods for placinga bandage structure within a body lumen or hollow body organ in anon-invasive way using endoscopic visualization.

The systems and methods do not involve the use of any sharp edges orpoints. The systems and methods do not involve the use of a pointpressure, as existing treatment options require. Only moderatecircumferential pressure is required to apply the bandage structure. Thesystems and methods adapt well to tools and techniques usable bygastroenterologists.

The systems and methods can be sized and configured to apply a chitosanbandage structure within a body lumen or hollow body organ, to takeadvantage of the mucoadhesive, antimicrobial, hemostatic, and potentialaccelerated wound healing properties of the chitosan material. Drugdelivery and cell therapy with a chitosan bandage structure as adelivery matrix are also made possible.

Other features and advantages of the invention shall be apparent basedupon the accompanying description, drawings, and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plane view of an intraluminal delivery system forintroducing and applying a bandage structure within a body lumen orhollow body organ.

FIG. 2 is perspective view of the bandage structure that is sized andconfigured for deployment by the system shown in FIG. 1.

FIGS. 3 to 5 show the rolling of the bandage structure into a lowprofile condition prior to deployment by the system shown in FIG. 1.

FIGS. 6 to 9 show the placement of a rolled bandage structure upon theexpandable delivery structure that forms a part of the system shown inFIG. 1.

FIGS. 10 to 13 show the use of the delivery system shown in FIG. 1 forintroducing and applying a bandage structure within a body lumen orhollow body organ.

FIG. 14 shows an optional over-tube that can be used in association withthe system shown in FIG. 1.

FIG. 15 shows the system shown in FIG. 1 hack-loaded into the workingchannel of an endoscope.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Although the disclosure hereof is detailed and exact to enable thoseskilled in the art to practice the invention, the physical embodimentsherein disclosed merely exemplify the invention, which may be embodiedin other specific structure. While the preferred embodiment has beendescribed, the details may be changed without departing from theinvention, which is defined by the claims.

I. The Intraluminal Delivery System

FIG. 1 shows an intraluminal delivery system 10 for introducing andapplying a bandage structure 12 within a body lumen or hollow bodyorgan. The delivery system 10 includes a bandage structure 12 and adelivery device 14 that is sized and configured to deliver and deploythe bandage structure 12 at a targeted tissue region within a body lumenor hollow body organ. The delivery device 14 is sized and configured todeploy the bandage structure 12 while preventing it from contactingtissue lining the body lumen or hollow body organ until the desired timeof deployment. The delivery device 14 not only provides a barrierbetween the bandage structure 12 and tissue within the body lumen orhollow body organ during introduction, but also provides a means todeploy the bandage structure 12 into contact with the tissue at thedesired time.

As shown in FIG. 1, the delivery device 14 can be sized and configuredto accommodate passage over a guide wire 32. In this way, the deliverydevice 14 can be introduced over the guide wire 32 under directvisualization from an endoscope 50, as FIG. 10 shows. In thisarrangement, the guide wire 32 runs next to the endoscope 50 andtherefore leaves the working channel of the endoscope 50 free. In analternative arrangement (see FIG. 15), the delivery device 14 can besized and configured to be back-loaded through the working channel 52 ofan endoscope 50. The working channel 52 of the endoscope 50 therebyserves to guide the delivery device 14 while providing directvisualization.

A. The Tissue Bandage Structure

The size, shape, and configuration of the bandage structure 12 shown inFIG. 1 can vary according to its intended use, which includes takinginto account the topology and morphology of the site to be treated andthe age/status of the patient (e.g., adult or child). The tissue bandagestructure 12 is desirably flexible and relatively thin so that it can berolled or folded upon itself for deployment in a low profile condition,as FIGS. 2 to 5 show. The tissue bandage structure 12 can berectilinear, elongated, square, round, oval, or a composite or complexcombination thereof. The shape, size, and configuration of tissuebandage structure 12 can be specially formed and adapted to the topologyand morphology of the site of application, by cutting, bending, ormolding in advance of use.

The tissue bandage structure 12 desirably includes an active therapeuticsurface 36 for contacting tissue. The active surface 36 desirablycomprises a biocompatible material that reacts in the presence of blood,body fluid, or moisture to become a strong adhesive or glue. Thematerial of the active surface 36 can, alone or in combination withadhesive features, possess other beneficial attributes, for example,anti-bacterial and/or anti-microbial and/or anti-viral characteristics,and/or characteristics that accelerate or otherwise enhance coagulationand the body's defensive reaction to injury.

In one embodiment, the material of the active surface 36 of the tissuebandage structure 12 comprises a hydrophilic polymer form, such as apolyacrylate, an alginate, chitosan, a hydrophilic polyamine, a chitosanderivative, polylysine, polyethylene imine, xanthan, carrageenan,quaternary ammonium polymer, chondroitin sulfate, a starch, a modifiedcellulosic polymer, a dextran, hyaluronan or combinations thereof. Thestarch may be of amylase, amylopectin and a combination of amylopectinand amylase.

In a preferred embodiment, the biocompatible material of the activesurface 36 comprises a non-mammalian material, which is most prefrablypoly [β-(1-4)-2-amino-2-deoxy-D-glucopyranose, which is more commonlyreferred to as chitosan.

The chitosan material is preferred because of the special properties ofthe chitosan. The chitosan active surface 36 is capable of adhering to asite of tissue injury along a body lumen in the presence of blood, orbody fluids, or moisture. The presence of the chitosan active surface 36stanches, seals, and/or stabilizes the site of tissue injury, whileestablishing conditions conducive to the healing of the site.

The chitosan material that is incorporated into the active surface 36can be produced in conventional ways. The structure or form producingsteps for the chitosan material are typically carried out from achitosan solution employing techniques such as freezing (to cause phaseseparation), non-solvent die extrusion (to produce a filament),electro-spinning (to produce a filament), phase inversion andprecipitation with a non-solvent (as is typically used to producedialysis and filter membranes) or solution coating onto a preformedsponge-like or woven product. The filament can be formed into anon-woven sponge-like mesh by non-woven spinning processes. Alternately,the filament may be produced into a felted weave by conventionalspinning and weaving processes. Improved compliance and flexibility canbe achieved by mechanical manipulation during or after manufacture,e.g., by controlled micro-fracturing by rolling, bending, twisting,rotating, vibrating, probing, compressing, extending, shaking andkneading; or controlled macro-texturing (by the formation of deep reliefpatterns) by thermal compression techniques. The tissue bandagestructure 12 can also comprise a sheet of woven or non-woven meshmaterial enveloped between layers of the chitosan material.

The active surface 36 that includes chitosan material presents a robust,permeable, high specific surface area, positively charged surface. Thepositively charged surface creates a highly reactive surface for redblood cell and platelet interaction. Red blood cell membranes arenegatively charged, and they are attracted to the chitosan material. Thecellular membranes fuse to chitosan material upon contact. A clot can bethrmed very quickly, circumventing immediate need for clotting proteinsthat are normally required for hemostasis. For this reason, the chitosanmaterial is effective for both normal as well as anti-coagulatedindividuals, and as well as persons having a coagulation disorder likehemophilia. The chitosan material also binds bacteria, endotoxins, andmicrobes, and can kill bacteria, microbes, and/or viral agents oncontact.

B. The Delivery Device

As FIG. 1 shows, the delivery device 14 includes a multi-lumen cathetertube 16 having a proximal end 18 and a distal end 20. The distal end 20carries an expandable structure 22, which in the illustrated embodimenttakes the form of an inflatable balloon. Other non-inflatable, butnevertheless expandable or enlargeable structures, can be used. Theproximal end carries an actuator 30 and a coupling 24 which aremanipulated in synchrony during operation of the expandable structure22, as will be described in greater detail later.

The catheter tube 16 can be formed of conventional polymeric materialsand include an interior lumen (not shown) that accommodates passage of aguide wire 32. The lumen also passes through the center of theexpandable structure 22 as well. This makes it possible to guide theintraluminal deployment of the expandable structure 22 to an injury sitewithin a body lumen or hollow body organ targeted for treatment.

The catheter tube 16 includes another lumen that communicates with theinterior of the balloon 22. The proximal end 18 of the catheter tube 16includes a coupling 24 for coupling an inflation device 26, such as asyringe or the like (see FIG. 1), in communication with the interior ofthe expandable structure 22. Operation of the inflation device 26conveys an appropriate inflation medium (e.g., saline) into theexpandable structure 22 to cause it to expand.

The catheter tube also includes a movable sheath 28. The sheath 28comprises a material that is flexible and impermeable to water. Apush-pull wire 30 is coupled to the sheath 28, which extends throughanother lumen within the catheter tube 16 and is coupled to an actuator30 on the proximal end 18 of the catheter tube 16. Pushing on theactuator 30 advances the sheath 28 distally over the expandablestructure 22 (as shown in phantom lines in FIG. 1). Pulling on theactuator 30 withdraws the sheath 28 proximally and free of theexpandable structure 22 (as shown in solid lines in FIG. 1).

In use, the tissue bandage structure 12 is sized and configured to becarried about the expandable structure 22 in a generally collapsedcondition during introduction within the body lumen or hollow body organ(see FIG. 10). The tissue bandage structure is also sized and configuredto be enlarged in response to expansion of the expandable structure 22(see FIG. 12) for placement into contact with tissue in the body lumenor hollow body organ.

FIGS. 2 to 5 show a representative embodiment of a flexible chitosanbandage structure 12 that can be readily deployed using the deliverydevice 14 in the manner just described. The bandage structure 12includes an inert, non-stick, water impermeable coating 34 on a sideopposite to the active chitosan surface 36. In use, it is the activechitosan surface 36 that is placed into contact with tissue. The inert,non-stick, water impermeable coating 3.4 makes it possible to roll orfold the chitosan surface 34 about the expandable structure 22 fordeployment without sticking or adhering to the expandable structure 22or itself.

Prior to intraluminal introduction of the delivery device 14 (see FIGS.6 and 7), the sheath 28 is withdrawn, and the chitosan bandage structure12 is mounted about the expandable structure 22, with the activechitosan surface 36 facing outward. In the illustrated embodiment, thisis accomplished by wrapping the chitosan bandage structure 12 around theexpandable structure 22, with the non-stick coating 34 facing theexpandable structure 22. This corresponds to the generally collapsedcondition described above, which provides a low profile condition forintraluminal introduction of the chitosan bandage structure 12.

In this arrangement, the flexible bandage structure 12 (see FIGS. 2 to5) has a rectangular shape with a tab 40 at one end. To secure thebandage in a rolled position about the expandable structure 22 (as shownin FIGS. 6 and 7), the tab can be inserted into a slit 42 formed in thechitosan bandage structure 12. The frictional force between the tab 40and the walls of the slit 42 are sufficient to hold the bandagestructure 12 in a rolled position. However, when pressure is appliedfrom within the rolled bandage structure 12 (as is shown in FIG. 12 andwill be described later), the tab 40 slides out of the slit 42 and thebandage structure 12 unfurls. Alternatively, the tab 40 and slit 42 canbe replaced by a biodegradable tape with a perforation that will be morereliable in preventing premature deployment or unfurling of the bandagestructure 12.

Prior to intraluminal introduction, the sheath 28 is advanced over thebandage structure 12 that has been wrapped about the expandablestructure 22 (see FIGS. 8 and 9). As FIG. 9 shows, the distal end of thesheath 28 is closed by a frangible or otherwise releasable securingdevice 44. The securing device 28 holds the distal end of the sheath 28closed.

The securing device 44 can be variously constructed. It can, e.g.,comprise a removable slip-knot that releases when the sheath iswithdrawn, or a tearable perforated tab that tears when the sheath iswithdrawn, or a ring that slides off or breaks when sheath is withdrawn.

In this position, the sheath 28 prevents contact between the activechitosan surface 36 and the mucosa during introduction until theinstance of application. The sheath 28 protects the bandage structure 12from becoming moist until the sheath 28 is moved proximally to revealthe bandage structure 12.

Prior to insertion into the body lumen (see FIG. 8), the expandablestructure 22 is desirably partially enlarged by introduction of theinflating media (e.g., to about 0.25 atm) to create bulbous forms oneach side of the bandage structure 12 as shown in FIG. 8. This partialexpansion prevents the bandage structure 12 from migrating from thecenter of the expandable structure 22 during the introduction, but doesnot otherwise unfurl the bandage structure 12, which remains in thegenerally collapsed condition.

As will also be described later, when it is desired to deploy thebandage structure 12, the sheath 28 is withdrawn (see FIG. 11) andsubsequent expansion of the expandable structure 22 (see FIG. 12)provides enough force to unfurl the bandage structure 12 into contactwith an interior wall of the body lumen or hollow body organ.

II. Use of the Delivery System

The delivery system 10 makes possible the deployment of a chitosanbandage structure 12 within a body lumen or hollow body organ underendoscopic visualization, e.g., to treat an injury of the esophagus orother area of the gastrointestinal tract.

As FIGS. 6 to 9 show, the chitosan bandage structure 12 can be wrappedand secured around the expandable structure 22 and enclosed duringintroduction with the removable sheath 28. The delivery device 12 can bedeployed either over a guide wire 32 alongside an endoscope 50 (as FIG.10 shows) or through the working channel of an endoscope (as FIG. 15shows). Once the chitosan bandage structure 12 is positioned correctlyover an injury site, the removable sheath 28 is pulled back (see FIG.11) to uncover the chitosan bandage structure 12 for deployment.Subsequent expansion of the expandable structure 22 (see FIG. 12)expands and unfurls the chitosan bandage structure, holding it againstthe mucosa circumferentially at the site of injury. After an appropriateholding time (e.g., about three minutes), the expandable structure 22 iscollapsed, and the delivery device 14 is withdrawn (see FIG. 13),leaving the chitosan bandage structure 12 at the injury site. During theentire procedure, the endoscope 50 provides direct visualization.

As the chitosan bandage structure 12 unfurls, it covers acircumferential section of the body lumen or hollow body organ andadheres to it. The properties of the active chitosan surface 36 serve tomoderate bleeding, fluid seepage or weeping, or other forms of fluidloss, while also promoting healing. Due to the properties of thechitosan, the active surface 36 can also form an anti-bacterial and/oranti-microbial and/or anti-viral protective barrier at or surroundingthe tissue treatment site within a body lumen or hollow body organ. Theactive surface 36 (whether or not it contains a chitosan material) canalso provide a platform for the delivery of one or more therapeuticagents into the blood stream in a controlled release fashion. Examplesof therapeutic agents that can be incorporated into the active surface36 of the bandage structure 12 include, but are not limited to, drugs ormedications, stem cells, antibodies, anti-microbials, anti-virals,collagens, genes, DNA, and other therapeutic agents; hemostatic agentslike fibrin; growth factors; Bone Morphogenic Protein (BMP); and similarcompounds.

The system 10 thereby makes possible an intraluminal delivery methodthat (i) locates and identifies the site of injury using an endoscope 50and correlating video monitor; (ii) passes a guide wire 32 into the siteof injury; (iii) positions the distal end of the delivery device 14 overthe guide wire 32 (see FIG. 10) at the site of injury while viewing thearea with the endoscope 50, which is positioned alongside the cathetertube 14; (iv) when positioned over the site of injury, as confirmed bythe endoscope 50, pulls the actuator 30 on the proximal end of thecatheter tube 14 (see FIG. 11) to withdraw the sheath 28 (also therebybreaking or otherwise releasing the security device 44) to unsheath andexpose the chitosan bandage structure 12; (v) expands the expandablestructure 22 (e.g., inflate the balloon) for a prescribed period (e.g.,about three minutes) (see FIG. 12) to unfurl the bandage structure 12and hold the active surface 36 of the bandage structure 12 againstmucosa; (vi) after the prescribed holding period, collapses theexpandable structure 22 (e.g. deflate the balloon) and removes thedelivery device 12 and guide wire 32 (see FIG. 13), while continuing tomonitor with the endoscope 50, if desired.

Various modifications of the above-described method can be made. Forexample (see FIG. 14), between (ii) and (iii), an over-tube 52 may beinserted in the body lumen to serve as a delivery sheath as well as afurther water impermeable barrier between the device and the mucosa. Asanother example (see FIG. 15), the actuator 30 and coupling 24 can beseparated from the proximal end of the catheter tube 14, and thecatheter tube 14 back-loaded (proximal end first) through the workingchannel 52 of an endoscope 50. Once back-loaded, the proximal componentsare re-connected to the catheter tube 14. This arrangement uses theworking channel 52 of the endoscope as a delivery sheath, instead of orin combination with a guide wire and/or an over-tube.

The shape, shape, and configuration of the expandable body and thebandage structure 12 can modified to accommodate varying anatomiesencountered within a body lumen or hollow body organ, such as thegastrointestinal tract. This expands the possible use of the deliverysystem 110 greatly. For example, in esophagogastrectomies, ananastomosis between the stomach and the esophagus is created where anasymmetric expandable structure 22 and a bandage structure 12 can bedeployed by the system 10 to cover the suture lines of the anastomosis.In addition, the size and shape of the expandable structure 22 can bealtered to accommodate deployment of a bandage structure 12 in theduodenum or stomach.

The intraluminal delivery method as described utilizes thecatheter-based delivery device 12, as described, to introduce aflexible, relatively thin chitosan bandage structure 12, as described,in an low profile condition and covered with a water impermeable layerto a targeted treatment site within a body lumen or hollow body organ,e.g. to treat esophageal injury. The delivery method prevents the activechitosan surface 36 of the bandage structure 12 from contacting themucosa until the bandage structure 12 positioned in a desired positionover the injury,

III. Conclusion

It has been demonstrated that a therapeutic bandage structure can beintroduced and deployed within a body lumen or hollow body organ usingan intraluminal delivery system 10 under endoscopic guidance.

It should be apparent that above-described embodiments of this inventionare merely descriptive of its principles and are not to be limited. Thescope of this invention instead shall be determined from the scope ofthe following claims, including their equivalents.

We claim:
 1. An intraluminal or hollow body organ bandage structuredelivery system comprising: a rolled chitosan bandage having a tab and aslit located on an outer surface, wherein the tab is slidably insertedinto the slit to hold the bandage in a rolled position; an expandablestructure supporting the bandage; and a removable sheath enclosing thebandage.
 2. The delivery system of claim 1, wherein the outer surface ofthe bandage provides an active surface that reacts in the presence ofbody fluid to become adhesive.
 3. The delivery system of claim 1,wherein the inner surface of the bandage provides a non-stick coating.4. The delivery system of claim 3, wherein the inner surface of thebandage is water impermeable.
 5. The delivery system of claim 1, whereinthe removable sheath includes a releasable securing device.
 6. Thedelivery system of claim 1, further comprising a multi-lumen cathetertube.
 7. The delivery system of claim 1, further comprising endoscopicvisualization.
 8. The delivery system of claim 1, further comprising aguide wire.
 9. A rolled chitosan bandage structure sized and configuredto be deployed within a body lumen or hollow body organ, wherein saidstructure comprises on a first side an outer surface comprising chitosanand including a tab and a slit formed therein and, on a second oppositeside, a non-stick coating.
 10. The rolled chitosan bandage of claim 9,wherein the tab is slidably inserted into the slit.
 11. The rolledchitosan bandage of claim 9, wherein the non-stick coating on the secondopposite side of said structure is water impermeable.
 12. A method fordelivery of a bandage structure within a body lumen or hollow bodyorgan, comprising: providing the delivery system of claim 1; positioningthe delivery system within the body lumen or hollow body organ andrelative to an injury site; and adhering the bandage to the injury site.13. The method of claim 12, further comprising: expanding the expandablestructure to apply pressure from within the bandage so that the tabslides out of the slit and the bandage unfurls.
 14. The method of claim12, further comprising: removing the expandable structure; and leavingthe bandage adhered to the injury site.
 15. A delivery system fordelivering a rolled chitosan bandage structure sized and configured tobe deployed within a body lumen or hollow body organ, wherein saidbandage structure comprises on a first side an outer active chitosansurface and, on a second opposite side, a non-stick coating, thedelivery system comprising a multi-lumen catheter tube having a proximalend and a distal end, the catheter tube comprising an interior lumenthrough which a guide wire is configured to pass, the distal endcarrying an expandable structure through which the interior lumenextends, the bandage structure being carried about the expandablestructure, and the catheter tube further comprising a removable sheath.16. The delivery system of claim 15, further comprising endoscopicvisualization.
 17. The delivery system of claim 15, further comprising apush-pull wire.
 18. The delivery system of claim 15, wherein theexpandable structure is partially enlarged to create bulbous forms oneach side of the bandage structure.
 19. The delivery system of claim 15,wherein the sheath has a releasable securing device at the distal end.20. The delivery system of claim 15, wherein the non-stick coating ofthe second opposite side of said bandage structure is water impermeable.